PROJECT 3 - Abstract Important issues in the development of psychopathology will be addressed in a longitudinal study of infants exposed prenatally to their mothers' depression, stress, and anxiety. These women and their husbands/partners will be participants in the proposed translational research center, Perinatal Stress and Gene Influences: Pathways to Infant Vulnerability. We have the unique opportunity to take advantage of the extensive prospective data that will have been collected throughout pregnancy, including measures of depression, stress, anxiety, use-of antidepressant medication (Core B), and fetal activity (Project 1) as well as genotyping for the 's' allele of the 5HT TLPR polymorphism in the infants and their parents (Project 2). In recognition of the unique aspects of the proposed dataset and the opportunities it presents for answering emerging questions, we propose to test hypotheses that promise to reveal the best model for understanding the most likely risk factors, mediators, and moderators in the transmission of risk for psychopathology in children born to women who were depressed during pregnancy. The Goodman and Gotlib (1999) model for the transmission of psychopathology to children of depressed mothers describes multiple mechanisms of risk whereby all of the infants in the proposed sample are at an increased risk for depression and other problems, relative to children whose mothers have not been depressed in pregnancy, and some are predicted to be at higher risk than others as a function of varying levels of genetic risk, adverse fetal environment, inadequate early maternal care, and father involvement. We propose to test hypotheses derived from this model in the prediction of the developmental course in the emergence (and continuity/discontinuity) of theory- and empirically-based measures of vulnerabilities for the development of psychopathology as they can be observed in infants. Assessments through the infants' first year will include measures of neuroendocrine, behavioral, and psychophysiological functioning. In order to take into consideration any added exposure to maternal depression, quality of maternal care, and the role fo the father, these constructs will also be measured. We will empirically derive the "best" set of predictors in a set of infant outcomes that have theoretical and empirical links implicating high risk for the later development of psychopathology. The understanding of such roles will be used to delineate guidelines for clinical interventions.